Antimicrobial containing solventless hot melt adhesive composition

ABSTRACT

An adhesive composition having dispersed therein a broad spectrum antimicrobial agent for use in medical applications, such as an adhesive for surgical drapes, wound dressings and tapes. The adhesive is composed of acrylic polymers, tackifiers and a preferred antimicrobial agent, diiodomethyl-p-tolylsulfone. The adhesive composition is essentially solventless and capable of application in a hot melt process while maintaining stability at elevated temperatures in the range of 275° F. to 350° F., which not only allows hot melt application, but allows for ethylene oxide sterilization under heat stress.

TECHNICAL FIELD

[0001] The present invention relates to a medical grade,antimicrobial-containing adhesive particularly suited for use in skincontact applications, such as with surgical drapes, tapes and wounddressings. More particularly, the adhesive compound is essentially a100% solids or essentially solventless hot melt adhesive incorporatingan acrylic polymer in conjunction with diiodomethyl-p-tolylsulfone as anantimicrobial agent.

BACKGROUND OF THE INVENTION

[0002] It is recognized that numerous pathogens are present on humanskin. Therefore, in a hospital environment, it is generally desired thatthe growth of disease-producing microorganisms be inhibited, andpreferably that these microorganisms be destroyed so as to controlpatient infection and encourage wound healing. Under most circumstances,the bacteria of normal skin cannot cause wound infections, but in thepresence of foreign materials or open wounds, the pathogenic potentialof these bacteria appears to be considerably enhanced. Furthermore, thelikelihood of bacterial contamination is at a peak immediatelypreceding, during, and following surgical procedures. Accordingly, toprevent contamination, it is imperative that the skin be effectivelydisinfected before a surgical incision is made and during the entiresurgical procedure.

[0003] In response to such concerns, many topical antimicrobial agentshave been developed. These agents typically are in the form ofpreoperative skin preps, surgical scrub tissues, washes, wound cleaners,lotions and ointments. A recognized limitation to such topicalapplications are a short effective delivery time. Microorganisms thatmay have survived the initial application of such a topicalantimicrobial agent can act as a seed, causing the pathogen populationin some instances to regenerate or rise to their initial levels. Thus,continuous application of an antimicrobial agent to the site isrecognized as a means of inhibiting this increase in population.

[0004] It has been recognized that a continuous or longer lastingantimicrobial effect may be achieved by incorporating the antimicrobialagent into an adhesive layer or into a surgical incise drape materialitself.

[0005] Berglund et al. (U.S. Pat. No. 4,310,509) disclose that it isknown to incorporate biologically active agents into adhesive layers ona substrate to provide continuous application of such agent to the body.Disclosed examples of known adhesives containing antimicrobial agentsinclude U.S. Pat. No. 2,137,169, wherein phenol, thymol, methanol, etc.are added to a starch adhesive; U.S. Pat. No. 3,249,109 where benzocainewas added to a tacky gelatin; U.S. Pat. No. 3,632,740 where acorticosteroid is added to an adhesive; U.S. Pat. No. 3,734,097 where amicroencapsulated anti-neoplastic agent is added to an adhesive; U.S.Pat. No. 4,073,291 where Tretinoin is added to an adhesive; U.S. Pat.No. 3,769,071 where 5-fluorouracil is incorporated into an adhesive; andU.S. Pat. No. 3,896,789 where retinoic acid is incorporated into apressure-sensitive adhesive tape. Berglund et al. further teach that theprior art attempts to include an antimicrobial agent in an adhesive didnot include the use of a broad spectrum antimicrobial because suchadhesives had been frustrated by uncontrollable release of the agentwith accompanying skin irritation in some patients, along with failureto obtain sufficient antimicrobial activity.

[0006] Berglund et al. disclose a pressure sensitive adhesivecomposition which contains chlorhexidene, polyvinylpyrrolidone iodine oriodine which is applied onto a polymer sheet material, such aspolyethylene or polyurethane, for use as a surgical drape. The discloseddrape is applied to the skin with the adhesive side contacting the skinso that the antimicrobial agent can be released from the adhesive to thewound area prior to and during incision. The process for making theadhesive disclosed by Berglund et al. involves forming an emulsifiableconcentrate or an organic solution concentrate of a broad spectrumantimicrobial agent and mixing it into an adhesive, such that the broadspectrum antimicrobial is homogeneously dispersed as a separate phasethroughout the adhesive medium. The homogenous dispersion is then spreador coated to a substantially uniform layer followed by drying of the wetlayer in order to remove the solvents.

[0007] Rosso et al. (U.S. Pat. No. 4,323,557) disclose a drapeincorporating a pressure sensitive adhesive utilizingn-vinylpyrrolidione residues in the polymer backbone. Iodine iscomplexed with these residues to provide an antimicrobial effect. Rossoet al. espouse the stability of the adhesive composition over the priorart compositions. By stable, Rosso et al. asserts that a compositioncoating of 11 grains per 24 sq. in. which is attached to a polyethylenesheet can be exposed to a temperature of 120° F. and a relative humidityof 9% for two weeks or to a dose of 2.5 megarads of gamma irradiationwithout substantial alteration of the physical appearance or of thechemical activity as tested by the starch test and microbiologicalactivity as tested by the zone inhibition assay. The disclosure of Rossoet al. is incorporated herein by reference.

[0008] The process for forming the adhesive composition disclosed byRosso et al. involves forming a pressure-sensitive adhesive and mixinginto it an antimicrobial treating solution comprising iodine, an iodide,and a solvent. The resulting composition preferably containsn-vinylpyrrolidone in the backbone of the pressure-sensitive adhesivewhich serves to complex the iodine. Rosso et al. disclose that thecomposition may be either attached directly onto a flexible backingsubstrate or formed onto a release liner for later use. Once applied,the solvents are then evaporated by means known to the art, whereby anadhesive film is formed which is useable in or on tapes, drapes andother medical devices.

[0009] Nixon et al. (U.S. Pat. No. 5,069,907) disclose a surgical drapehaving incorporated therein a broad spectrum antimicrobial agent. Thedrape comprises a synthetic polymeric film or fabric having incorporatedtherethrough an amount of antimicrobial agent. The drape may optionallyhave an adhesive layer attached to one of its external surfaces, whereinthe adhesive layer can have dispersed therethrough an antimicrobialagent. The preferred antimicrobial agent used is5-chloro-2-(2,4-dichlorophenyl)phenol. Suitable adhesives utilizedinclude polyacrylate adhesives.

[0010] Mixon et al. disclose a large number of antimicrobial agentswhich were contemplated for use with the disclosed composition. Theseinclude metal salts, typical antibiotics, antibacterial agents such aschlorhexidine and its salts, quaternary ammonium compounds, iodophorssuch as povidone iodine, acridine compounds, biguanidine compounds, anda preferred antimicrobial agent 5-chloro-2-(2,4-dichlorophenoxy)phenol.Mixon et al. further disclose that these same antimicrobial agents,which they propose to utilize within the polymer composition for theirsurgical drape, can also be utilized in an adhesive composition. Mixonet al. further state that the antimicrobial agent can be directlyapplied to the surgical drape in solution as an aqueous dispersion, as ahot melt, or by a transfer process using known techniques, such asknife, roller-coating, or curtain-coating methods. The transfer processis disclosed as particularly preferred. In a transfer process, theadhesive emulsion, including water or a different solvent, optionallycontaining an antimicrobial agent, is spread onto a sheet of releasepaper and dried to remove the water or solvent. The surgical drape isthen brought into contact with the adhesive and calendared to insurethat the adhesive adheres to the drape. The surgical drape will thengenerally include a release sheet covering the adhesive, and the releasesheet on which the adhesive is deposited can be used for that purpose,or that release sheet can be removed and replaced with another releasesheet. In embodiments where the adhesive contains an antimicrobialagent, the mixture of adhesive and antimicrobial agent is dried aftercoating on the release sheet, and the antimicrobial agent remainsdispersed in the adhesive.

[0011] Generally, presently known antimicrobial agents are limited intheir ability to withstand heat during processing. The lack of heatstability of n-vinyl pyrrolodione iodine has limited the ability fordrapes having this antimicrobial agent from being ethylene oxidesterilized under heat stress. Further, many of the antimicrobialcompounds cannot be radiation sterilized. Thus, each prior art referenceteaches that it is preferred to apply the antimicrobial adhesive inconjunction with a solvent followed by subsequent evaporation of thesolvent.

[0012] Accordingly, the need exists for an adhesive composition havingan antimicrobial agent dispersed therethrough which is heat stable andsolventless. Such composition would eliminate the need for use ofsolvents with their potential environmental effects and would eliminatethe need for removing such solvent from the adhesive after applicationto the drapes. Further, the heat stability would allow the solventlessadhesive to be applied in a hot melt process, while also allowing forethylene oxide sterilization under heat stress or radiationsterilization.

SUMMARY OF THE INVENTION

[0013] The present invention is an adhesive composition having a broadspectrum antimicrobial agent dispersed therethrough. The adhesivecomposition is an essentially solventless composition (100% solids),which is heat stable so that it may be applied in a hot melt process,while also being capable of ethylene oxide sterilization under heatstress without loss of effectiveness of the antimicrobial agent.Specifically, the adhesive is for skin-contact applications, forexample, surgical drapes, tapes and wound dressings. The antimicrobialagent utilized is diiodomethyl-p-tolylsulfone with a preferredconcentration of antimicrobial agents in the adhesive of about 0.1% toabout 2% loading by weight.

[0014] The antimicrobial agent is homogeneously dispersed through theadhesive layer. Active antimicrobial molecules continually disassociatefrom the surface or leach out of the adhesive matrix over time,delivering biocidal activity at a distance from the adhesive surface.Applicants have conclusively demonstrated this property by zone ofinhibition tests on a wide variety of infectious organisms. These testsconclusively showed that microbes were inhibited at a distance from thesample.

[0015] Adhesive compositions can incorporate acrylic or rubber basedpolymers to form the hot melt adhesive. A preferred composition includesa mixture of two acrylic polymers, one of which is a low molecularweight solid acrylic polymer, the other a medium molecular weight solidacrylic polymer, which are both designed for hot melt pressure-sensitiveadhesive applications. A low molecular weight solid acrylic polymer isavailable from Schenectady International, Inc. as Product No. HRJ-4326,and a medium molecular weight solid acrylic polymer is also availablefrom Schenectady International, Inc. under Product No. HRJ-10127.Tackifiers can also be added to the adhesive composition as is wellknown in the art.

[0016] The present adhesive composition is a hot melt adhesive. By hotmelt adhesive, it is meant that the adhesive is essentially solventlessor 100% solids and is processed in liquid form at elevated temperaturesin the range of about 275° F. to 350° F. A preferred temperature rangefor compounding and coating the antimicrobial adhesive is 290° F. to320° F. The antimicrobial containing adhesive is manufactured by heatingthe adhesive composition to about 250° F., including both a lowmolecular weight acrylic polymer and a medium molecular weight acrylicpolymer along with any tackifiers to be utilized. The mixture is thenheated to about 310° F. to about 315° F. and mixed until uniform withsubsequent cooling to 290° F. to 295° F. at which point thediiodomethyl-p-tolylsulfone is added. The composition is mixed untiluniform with subsequent packaging and cooling. The composition may thenbe hot melted and applied as needed by the user.

[0017] In a preferred application, the antimicrobial adhesivecomposition of the present invention is utilized to overly a polymericsubstrate to form a surgical drape. The polymeric substrate ispreferably a polyester or co-polyester sheet material which may haveincorporated therein or coated on the side opposite the adhesive anantimicrobial agent.

[0018] These and various other advantages and features of novelty whichcharacterize the present invention are pointed out with particularity inthe claims annexed hereto and forming a part hereof. However, for abetter understanding of the invention, its advantages, and the objectsobtained by its use, reference should be made to the accompanyingdescriptive matter in which there are illustrated and describedpreferred embodiments of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] As required, detailed embodiments of the present invention aredisclosed herein. However, it is to be understood that the disclosedembodiments are merely exemplary of the present invention which may beembodied in various systems. Therefore, specific details disclosedherein are not to be interpreted as limiting, but rather as a basis forthe claims and as a representative basis for teaching one skilled in theart to variously practice the present invention.

[0020] The present invention is an adhesive compound which incorporatesan adhesive component together with a broad spectrum antimicrobial agentdispersed therethrough. The antimicrobial agent is homogeneouslydispersed throughout the adhesive layer. Active antimicrobial moleculesof the present composition disassociate from the surface or leach out ofthe adhesive matrix over time, delivering biocidal activity at adistance from the adhesive surface. Applicants have conclusivelydemonstrated by zone of inhibition tests on a wide variety of infectiousorganisms the efficacy of the present composition. These tests showedthat microbes were inhibited and killed at a distance from the sample asdetailed in the attached experimental examples.

[0021] The adhesive of the present invention is specifically suited foruse in skin contact applications during and after medical procedures,for example; as an adhesive in surgical drapes, wound dressings andtapes. The adhesive composition is a hot melt adhesive. By hot meltadhesive, it is meant that the adhesive is essentially solventless or100% solids and flowable at elevated temperatures for application to asubstrate material, such as a surgical drape. The preferred adhesivecomposition incorporates acrylic polymers and added tackifiers to form apressure-sensitive adhesive which is particularly suited for use insurgical procedures.

[0022] A preferred combination of acrylic polymers to form the adhesivecomposition includes the combination of a low molecular weight solidacrylic polymer and a medium molecular weight solid acrylic polymer in aratio of about 1 to 4, respectively, to optimize the adhesion of theadhesive to skin, cohesion and resistance to cold flow. A low molecularacrylic polymer is a polymer having a molecular weight ranging fromabout 90,000 to about 120,000, while a medium molecular weight acrylicpolymer has a molecular weight ranging from about 140,000 to about160,000. Suitable low molecular weight solid acrylic polymers and mediummolecular weight solid acrylic polymers are available from SchenectadyInternational, Inc. under Product Nos. HRJ-4326 and HRJ-10127,respectively.

[0023] The adhesive component of the composition can also includetackifiers as are well known in the art. Tackifiers contemplated includeSYLVATEC, ZONAREZ and FORAL which are available from Arizona Chemicaland Hercules, Inc.

[0024] As previously stated, the adhesive compound is a hot meltadhesive. A preferred composition has a feasible temperature range forworking with the hot melt adhesive in the range of about 275° F. to 350°F. The preferred temperature range for compounding and coating with theadhesive is 290° F. to 320° F.

[0025] Applicants have found that the addition of a heat stableantimicrobial agent to the above adhesive composition results in aneffective antimicrobial adhesive composition. In particular, Applicantshave found that the addition of diiodomethyl-p-tolylsulfone to the aboveadhesive composition results in an effective antimicrobial adhesivewhich retains desirable properties during use and application at 275° F.to about 350° F. A preferred loading of antimicrobial agent to theadhesive is in the range of about 0.1% to about 2% by weight. Apreferred loading is about 0.2% by weight to about 0.6% by weight ofdiiodomethyl-p-tolylsulfone to adhesive. The resulting heat stableantimicrobial containing adhesive is 100% solids and eliminates the needfor use of a solvent and the requisite evaporation of such solvent. Thehot melt adhesive can also be ethylene oxide sterilized under heatstress or radiation sterilized without loss of effectiveness of theantimicrobial.

[0026] A preferred source of diiodomethyl-p-tolylsulfone is AMICAL 48,available from Angus Chemical Company.

[0027] The antimicrobial containing adhesive composition of the presentinvention is manufactured by mixing thoroughly at elevated temperaturethe acrylic polymers and tackifiers. A temperature of about 250° F. toabout 260° F. has been found to be adequate. Once mixed, the polymersand tackifiers are heated to 310° F. to 350° F. with continued mixinguntil uniform, followed by cooling to 290° F. to 295° F. Thediiodomethyl-p-tolylsulfone is then added to the polymer and mixed untiluniform. The resultant composition is packaged and cooled for subsequenthot melt applications.

[0028] As detailed below, the antimicrobial adhesive of the presentinvention was shown to be effective against a wide variety ofmicroorganisms. The antimicrobial activity was determined by using aseries of zone of inhibition tests, as are well known in the art. Theeffective release of antimicrobial from the adhesive is estimated fromthe measurement of a zone of inhibition (an area of inoculated platewhere organisms do not grow) surrounding the sample.

[0029] The adhesive utilized for the tests included 2%diiodomethyl-p-tolylsulfone homogeneously dispersed as detailed above inan adhesive composition. The adhesive composition included 17% lowmolecular weight acrylic polymer (HRJ-4326 from SchenectadyInternational, Inc.) and 67% medium molecular weight polymer (HRJ-10127from Schenectady International, Inc.) along with 16% FLORAL 105synthetic resin from Hercules, Inc. as a tackifier. The adhesivecomposition was prepared as detailed above. The adhesive composition wasthen melted and applied to a substrate layer in a thin coating(approximately 0.05 mm in thickness). The substrate was a co-polyestersurgical drape material available from DuPont under the tradenameHYTREL. The coated substrate was cut to 6.0 mm disks for use in testing.

[0030] Adhesive coated disks were then exposed to microorganisms usingthe following procedure:

[0031] 1. A microbial suspension containing=1.0×10⁸ organisms per ml inTSB was compared to the turbidity of a 0.5 MacFarland Standard.

[0032] 2. A sterile swab was dipped into the culture suspension. Theswab was rotated several times, pressing firmly on the inside wall ofthe tube above the fluid level. This removed excess inoculum from theswab.

[0033] 3. The surface of a Mueller Hinton agar plate was inoculated bystreaking the swab over the entire sterile agar surface. This streakingprocedure was repeated two more times, rotating the plate approximately60° each time to ensure an even distribution of inoculum.

[0034] 4. The paper liner was removed from each 6 mm adhesive coateddisc and the film was aseptically placed adhesive side down on thesurface of the inoculated agar plate. Control samples were handledidentically.

[0035] 5. Immediately following the addition of the discs, the MuellerHinton agar plates were placed in ambient air at 35-37° for 18-24 hours.Following incubation, the zones of inhibition surrounding the discs weremeasured. When no zone was observed, the disc was aseptically removedand the area beneath the disc was evaluated for growth of the testorganism. The tests were repeated two or three times, using relevantmicroorganisms. Experimental results are presented in the table below,reported as the average diameter zone of inhibition surrounding/under6.0 mm samples. A 6.0 mm zone of inhibition indicates no growth of thetest organism beneath the 6.0 mm test discs, while larger zones indicateeffective antimicrobial activity at a distance from the disc. TABLE 1Test Organism Zone of Inhibition Staphylococcus aureus 12.0 mm  (ATCC6538) Escherichia coli 6.0 mm (ATCC 11229) Pseudomonas aeruginosa 6.0 mm(ATCC 15442) Klebsiella pneumoniae 7.0 mm (ATCC 4352) Pseudomonascepacia 6.0 mm (ATCC 25416) Enterobacter cloacae 6.0 mm (ATCC 13047)Serratia marcescens 6.5 mm (ATCC 14746) Streptococcus pyogenes 10.5 mm (ATCC 19615) Enterococcus faecalis- 9.5 mm Vancomycin Resistant (ATCC51299) Candida albicans 33.5 mm  (ATCC 10231) Bacillus subtilis 9.2 mm(ATCC 19659)

[0036] These results indicate that the present adhesive is effective ininhibiting these eleven relevant organisms, even after hot meltprocessing and ethylene oxide sterilization.

[0037] New characteristics and advantages of the invention covered bythis document have been set forth in the foregoing description. It willbe understood, however, that this disclosure is, in many respects, onlyillustrative. Changes may be made in details, particularly in matters ofshape, size, and arrangement of parts, without exceeding the scope ofthe invention. The scope of the invention is, of course, defined in thelanguage in which the appended claims are expressed.

What is claimed:
 1. A hot melt adhesive composition having antimicrobialproperties for skin contact applications comprising: a. an acrylicpolymer; and b. an effective amount of diiodomethyl-p-tolylsulfonedispersed throughout said polymer.
 2. The adhesive composition of claim1, wherein said acrylic polymer comprises a mixture of a low molecularweight solid acrylic polymer and a medium molecular weight solid acrylicpolymer.
 3. The adhesive composition of claim 2, wherein said lowmolecular weight acrylic polymer has a molecular weight between about90,000 and about 120,000 and said medium molecular weight acrylicpolymer has a molecular weight between about 140,000 and about 160,000.4. The adhesive composition of claim 2, wherein the ratio of lowmolecular weight polymer to medium molecular weight polymer is about 1to
 4. 5. The adhesive composition of claim 2, further comprising aneffective amount of a tackifier.
 6. The adhesive composition of claim 1,wherein the concentration of diiodomethyl-p-tolylsulfone in said polymercomposition is about 0.1% to about 2% by weight.
 7. The adhesivecomposition of claim 1, wherein said acrylic polymer has a melttemperature between about 275° F. and about 350° F.
 8. A hot meltadhesive composition having antimicrobial properties comprising: a. anessentially 100% solids acrylic polymer for hot melt application; and b.an effective amount of diiodomethyl-p-tolylsulfone dispersed throughoutsaid acrylic polymer.
 9. The adhesive composition of claim 8, whereinsaid acrylic polymer comprises a mixture of a low molecular weight solidacrylic polymer and a medium molecular weight solid acrylic polymer. 10.The adhesive composition of claim 9, wherein said low molecular weightacrylic polymer has a molecular weight between about 90,000 and about120,000 and said medium molecular weight acrylic polymer has a molecularweight between about 140,000 and about 160,000.
 11. The adhesivecomposition of claim 10, wherein the ratio of low molecular weightpolymer to medium molecular weight polymer is about 1 to
 4. 12. Theadhesive composition of claim 8, further comprising an effective amountof a tackifier.
 13. The adhesive composition of claim 8, wherein theconcentration of diiodomethyl-p-tolylsulfone in said polymer compositionis about 0.1% to about 2% by weight.
 14. The adhesive composition ofclaim 8, wherein said acrylic polymer has a melt temperature betweenabout 275° F. and about 350° F.
 15. A surgical drape comprising: a. asheet of polymeric substrate; b. a coating of an adhesive compositionoverlying said polymeric substrate wherein said adhesive composition ishot melt applied to said substrate and includes an acrylic polymerhaving an effective amount of diiodomethyl-p-tolylsulfone dispersedthroughout said adhesive composition.
 16. The surgical drape of claim 15wherein said substrate comprises a sheet of co-polyester.
 17. Thesurgical drape of claim 15, wherein said acrylic polymer comprises amixture of a low molecular weight solid acrylic polymer and a mediummolecular weight solid acrylic polymer.
 18. The surgical drape of claim17, wherein the ratio of low molecular weight polymer to mediummolecular weight polymer is about 1 to
 4. 19. The surgical drape ofclaim 15, wherein the concentration of diiodomethyl-p-tolylsulfone insaid polymer composition is about 0.1% to about 2% by weight.
 20. Thesurgical drape of claim 15, wherein said acrylic polymer has a melttemperature between about 275° F. and about 350° F.
 21. The surgicaldrape of claim 15 further comprising an antimicrobial agent applied tosaid surgical drape on the side opposite said coating of an adhesivecomposition.